DOPAMINE NEUROTRANSMISSION AND MORPHOLOGICAL CHANGES IN THE FOREBRAIN OF PRENATALLY STRESSED RATS

BARROS, VG; DUHALDE VEGA, M; CALTANA, L; BRUSCO, HA; SILVAGNI, A,; CARBONI, E; ANTONELLI, MC

Viña del Mar, Chile

Congreso; II Neurotoxicity Society Meeting; 2005

Variable stress applied during the las week of gestation was shown to produce long-term effects on the adult offsprings. Among other effects, prenatal stress (PS) increased the level of D2-type dopamine (DA) receptors and the vulnerability to drug of abuse such as amphetamine and nicotine in the adult offspring. Moreover, the reduction in right-sided rotation observed in PS rats was associated with an increase in dopamine turnover in the right prefrontal cortex (PFC) and a decrease in the left striatum in both sexes. In this study we measured the levels of DA and noradrenaline (NA) in brain microdialisys following nicotine or amphetamine injection to freely moving rats. Due to the possible influence of pubertal hormones, we performed this study in prepubertal (4 week) and adult (8week) prenatally stressed male offsprings. The results show that the level of DA and NA both in PFC and Nucleus Accumbens Shell (NAcS) of prenatally stressed rats were similar to those of control rats. However when amphetamine were injected subcutaneously, DA and NA concentration in dialysates were lower in PFC of prenatally stressed rats of 4 weeks old. The injection of nicotine also impairment the released of DA and NA in PFC and NAcS in prenatally stressed rats at both ages tested. This prepubertal impairment in DA release in response to an exogenous challenge in PFC might be explaining the elevated levels of dopamine receptor observed in the same region in the adult prenatally stressed offspring unless the overproduction of dendritic arborization and synapsis was nor properly pruned during the adolescent period of these rats. We therefore studied immunocytochemically different neuron and astrocytic markers. We found that MAP2 ( a microtubule associated protein present in dendrites) and synaptophysin ( a major integral protein of the synaptic vesicles membrane) were decreased in cerebral cortex and hippocampus, whereas GFAP (the main cytoskeletal astroglial protein) and S100b protein (an astroglial derived neurotrophic factor) were significantly increased implying the presence of reactive astrocytes and a reduced dendritic arborization. In summary, both NA and DA drug-induced released mechanisms appear to be impaired mainly in limbic areas of the prepubertal prenatally stressed rats that might lead to the increased DA receptor levels previously observed in adult rats.